Pediatric brain tumors, including high-grade gliomas (HHG), medulloblastomas (MB), and ependymomas (EPN), are a leading cause of death in children. They are often immunologically "cold" with low tumor mutational burden (TMB) and very few tumor-infiltrating lymphocytes (TILs), which may limit the role of immune checkpoint inhibitors (ICI). We performed a PRISMA‑guided systematic review of PubMed/MEDLINE, Embase, and Scopus from inception to September 17, 2025, for English-language studies of patients ≤ 21 years with primary CNS tumors treated with PD‑1/PD‑L1 or CTLA‑4 inhibitors. Eligible reports included prospective trials, retrospective series, and observational/case reports with extractable data on efficacy and/or toxicity. Of 479 records identified, 386 unique citations were screened, 127 underwent full‑text review, and 40 met inclusion criteria for qualitative synthesis. Prospective and institutional studies in biomarker-unselected diffuse midline glioma, high-grade glioma, medulloblastoma, and ependymoma showed low objective response rates (generally ≤ 6%), short median progression-free survival (1-3 months), and overall survival similar to historical controls, despite acceptable safety (grade ≥ 3 treatment-related adverse events ~ 15-25% with anti-PD-1 ± anti-CTLA-4). In contrast, across germline MMR-deficient and broader RRD/hypermutant cohorts, PD-1 blockade produced clinically meaningful and sometimes durable responses, including complete remissions in malignant glioma and approximate 2-year overall survival near 50%, often with delayed responses and pseudoprogression. Histology-specific profiling highlighted marked variation in immune contexture: pediatric gliomas segregate into immune "hot," "altered," and "cold" subtypes; medulloblastoma is largely PD-L1-low with prominent B7-H3 and myeloid programs; checkpoint expression is also observed in germ cell and selected sellar tumors. Evidence quality is limited by small, heterogeneous, predominantly non-comparative designs. ICIs show manageable safety but limited efficacy in unselected pediatric CNS tumors. Durable benefit is most evident in RRD/hypermutant biology and possibly PD-L1-high niches (e.g., some low-grade gliomas and CNS-GCT). Future trials should be biomarker-driven and pair ICIs with priming combinations (e.g., radiation, epigenetic modulators, metronomic chemotherapy) to convert "cold" tumors into responders.

Pneumocystis jirovecii causes a potentially fatal interstitial pneumonia, especially in immunosuppressed hosts. It was the most common cause of death in children with leukaemia, before the introduction of prophylaxis. In this study, we evaluated the clinical and demographic characteristics of proven PJP cases in children with haematological malignancy on chemotherapy. The study also determined the association of PJP characteristics with various phases of chemotherapy. This was a retrospective study conducted at a tertiary care teaching hospital in Delhi. Cases included 13 children less than 12 years of age with leukaemia on chemotherapy with proven PJP diagnosis, according to the EORTC/MSGERC guidelines. For microbiological diagnosis, direct immunofluorescence was performed using the Merifluor® Pneumocystis kit manufactured by Meridian Bioscience Inc. B-cell acute lymphoblastic leukaemia was the most common haematological malignancy seen in these cases. Most of the PJP cases were seen in the maintenance phase of chemotherapy. The clinical profile of the PJP cases includes fever, cough, cytopenia, hypoxaemia, coryza, dyspnoea, and hepatitis. The radiological findings of the PJP cases include bilateral diffuse ground-glass opacification, perihilar infiltrates, and unilateral infiltrates. The mortality rate of the PJP cases was 15.4%. Pneumocystis jirovecii causes a potentially life-threatening pneumonia, especially in immunocompromised individuals such as children with leukaemia on chemotherapy. PJP presents more severely with rapid progression and higher mortality rate in children with leukaemia than in HIV-positive cases. Therefore, early diagnosis and prompt treatment initiation is paramount in reducing morbidity and mortality in these cases.

Abusive head trauma is the most common cause of death in children suffering non-accidental injury (NAI). Intracranial haemorrhage can (rarely) be caused by inherited bleeding disorders. Evaluation of children with suspected NAI and intracranial bleeding involves diagnosis or exclusion of a bleeding disorder; however, there is a paucity of evidence to guide haematological evaluation in these patients. To determine the prevalence of inherited bleeding disorders in children with intracranial haemorrhage suspected of NAI and determine which tests have the highest diagnostic yield. We conducted a retrospective cohort study of children referred to the Child Protection Unit at Sydney Children's Hospital, Australia, between 2011 and 2020 with intracranial haemorrhage. Descriptive analyses of the data were completed. A total of 120 children were included in the cohort. Eighty-seven (73%) had a baseline coagulation screen (FBC, PT and APTT) performed with initial pathology testing within 72 h of presentation. Three children (2.5%) were identified to have an underlying inherited bleeding disorder, all of whom (100%) had a prolonged APTT on initial testing. An extensive array of haematological investigations was performed, but with a lack of consistency. Three patients were identified to have an inherited bleeding disorder, including haemophilia A, haemophilia B and von Willebrand disease, two of whom were confirmed NAI regardless. All three had abnormal APTT on the initial coagulation screen. We propose initial haematological screening with FBC, PT/APTT/fibrinogen only, unless bleeding risk factors are identified. If an abnormality is detected, subsequent factor levels and further haematological investigations are recommended.

Acute Respiratory Tract Infection (ARI) is an infectious disease that can affect the human respiratory system. ARI is an infection of the upper respiratory tract caused by microorganisms, including the nasal cavity, pharynx, and larynx, which lack gas exchange (Mustafa et al., 2023). An estimated 13 million people die from ARI. The disease burden varies widely, ranging from approximately 4 million of the 13 million people in India (48%), Indonesia (38%), Ethiopia (4.4%), Pakistan (4.3%), China (3.5%), Sudan (1.5%), and Nepal (0.3%). New ARIs occur in almost every region of the world. In 2022, Southeast Asia had the highest number of ARI cases worldwide. Approximately 30 countries contributed to the number of cases. (WHO, 2022) The incidence of acute respiratory infections (ARI) in Indonesia is relatively high, reaching 166,702 in 2022. This figure reaches 53% of the 50% target. Of this 53%, 31.4% of ARTI cases occur in toddlers. ARI is the second leading cause of death in children under five (12-59 months), accounting for 9.4%. This disease is an acute respiratory infection with symptoms of fever, cough lasting less than two weeks, runny nose/nasal congestion, and/or sore throat (Ministry of Health, 2022). In addition to medical treatment, ARTI treatment can also be supported by the use of natural ingredients. The combination of ginger and honey has been shown to have a synergistic effect in relieving ARTI symptoms. Red ginger (Zingiber officinale var. rubrum) is a herbal plant long known and used by Indonesians as a traditional medicine. Red ginger contains active compounds such as gingerol, shogaol, and zingerone, which have anti-inflammatory, antioxidant, and antimicrobial properties. These ingredients are useful in helping relieve symptoms of ARI, such as reducing inflammation in the respiratory tract, relieving coughs, and increasing the body's immune system.

Comparative medico-legal analysis of falls from height injuries in adults and children: Patterns and predictors of mortality.

Undernutrition significantly increases the risk of severe infections and mortality in children under five, particularly in low- and middle-income countries. Pneumonia, a leading cause of childhood death, is especially dangerous in undernourished children, yet prognostic measures to identify those at highest risk are lacking. To identify algorithms of poor prognosis in undernourished children with clinical pneumonia for early identification of children at risk for poor outcomes. This study analyzed a subset of children enrolled in a cohort designed to identify biomarkers of bacterial pneumonia. Children aged 2–59 months with clinical pneumonia were recruited from two rural Gambian hospitals. Clinical and anthropometric data were collected at baseline, during hospitalization, and at 30-day follow-up. Nutritional status was classified using WHO definitions for stunting (height-for-age Z-scores) and wasting (weight-for-height Z-scores) as severe (Z-scores ≤ -3), moderate (-2 ≥ Z-scores > -3), and mild (-1 ≥ Z-scores > -2). Prognostic outcomes were classified into good and poor. Poor prognosis included death, prolonged hospital stay (≥ 7 days), post-discharge care-seeking, and difficult to feed during admission. Good prognosis was based on a hospital stay < 3 days, with good outcomes within 30 days of the initial visit. Classification tree models and penalized logistic regression models (fit through elastic net) were used to identify combinations of predictors of poor prognosis (prognostic signatures). A total of 246 children with clinical pneumonia and undernutrition (wasting or stunting) were included. Children with poor prognosis presented more frequently with respiratory distress, hypoxemia, reduced capacity oforal feeding difficulty, and anemia. As expected, undernutrition was associated with adverse outcomes. The final prognostic algorithms were accurate to identify undernourished children at risk of poor prognosis: with sensitivity and specificity > 80% and area under the receiver operating characteristic curve ≥ 0.80. Furthermore, we identified accurate prognostic signatures among children with both wasting and stunting. Measures collected at admission in undernourished children with clinical pneumonia can identify those at risk of poor outcomes. The prognostic signatures developed in this study may inform early risk stratification and guide timely intervention, particularly in resource-limited settings.

A Dried Platelet-Derived Biologic for Blood-Brain Barrier Repair and Hemorrhage Control Following TBI in Mice.

Background: Diarrhea is a leading cause of childhood death in the world, account ing for 5-10 million deaths per year. Worldwide, rotavirus is estimated to cause more than 111 million cases of diarrhea annually in children younger than 5 year of age. It is considered as a major cause of childhood morbidity and mortality particu larly in developing countries like Bangladesh. Considering the high morbidity and significant mortality, this study was designed to determine the incidence of rotavirus and adenovirus associated diarrhea among under 2 years. Materials and methods: This cross-sectional study was conducted in the Department of Pediatric Gastroenterology, Chattogram Maa-O-Shishu Hospital Medical College from 1st September 2022 to 28th February 2023. Total of 150 patients were enrolled in this study who were admit with acute watery diarrhoea. Stool samples were obtained and assayed for rotavirus antigen by Immunochromatography Test (ICT) – ICT Quick Rotavirus kits (Arco Biotech, Germany) were used to detect rotavirus antigen in stool samples. Results: Viral antigens were detected in 116 (77.33%) out of 150 samples analysed during the study period. Of the antigen-positive samples,70(60.3%) belonged to boys and 46 (39.65%) belonged to girls. Of the total antigen-positive samples the Rotavirus antigen was identified in 101 (87.06%) specimens, the Adenovirus antigen was identified in 11 (9.48%) and Rota adeno was identified in 4 (3.44%) specimens. The high prevalence of rotavirus and adenovirus between the ages of 7 and 12 was found 47 (40.51%) and 6 (5.17%) respectively which is to be statistically significant (p &lt; 0.05). High incidence rate of rotavirus infections in winter months was determined. This was found to be statistically significant (p &lt; 0.05). Conclusion: This study showed a high prevalence of Rotavirus (67.33%) infection in patients under 2 years of age. Peak age incidence under 12 months and in January . Using the rotavirus vaccine in this population can reduce diarrhoea prevalence and eliminate unnecessary antibiotic use. Chatt Maa Shi Hosp Med Coll J; Vol.24 (2); July 2025; Page 97-101

Pediatric trauma: Where are we and where are we heading? A narrative review of recent evidence.

ABSTRACT Under nutrition is the main cause of child death in developing countries. The Composite Index of Anthropometric Failure (CIAF) combines all three forms of anthropometric failures to assess the nutrition status of children. Thus, the objective of this was to identify factors associated with CIAF of under‐five children in Lesotho. A secondary analysis of the Lesotho Demographic and Health Survey 2023–24 was conducted, using the data for 1089 children under the age of 5 years. The CIAF was used to classify children based on stunting, wasting, and underweight. Descriptive summary statistics were computed. A binary logistic regression model was employed to identify predictors of CIAF for under‐five children. Adjusted odds ratio with 95% confidence interval was estimated. The prevalence of CIAF in Lesotho was 34.68% (95% CI: 31.76–37.73). Female child 0.54 (AOR = 0.54; 95% CI: 0.375, 0.776), age group 24–59 months 2.42 (AOR = 2.42; 95% CI: 1.149, 5.109), rich households 0.29 (AOR = 0.29; 95% CI: 0.151, 0.554), multiple births 12.02 (AOR = 12.02; 95% CI: 1.199, 120.426), rural residence (AOR = 0.56: 95% CI: 0.335, 0.946), living children 3 to 4 were 2.54 (AOR = 2.54; 95% CI: 1.522, 4.226), and larger size at birth were 0.38 (AOR = 0.38; 95% CI: 0.211, 0.683) were found to be significantly associated with CIAF. The prevalence of CIAF among children under five in Lesotho was high. Child's age, child's sex, child's type of birth, wealth tercile, residence, number of living children, and child's birth size were found to be significantly associated with CIAF. We suggest that the government adapt CIAF as a metric for assessing children's nutritional status in order to estimate the overall prevalence of malnutrition and strengthening adequate nutrition intervention programs in rural areas. Furthermore, highlighting the factors influencing child CIAF will help inform future policies and programs designed to approach this major problem in Lesotho.

Inflammation is a major driver of preterm birth, a common pregnancy disorder and the leading cause of childhood death. T regulatory (Treg) cells are essential mediators of maternal fetal tolerance and are critical for constraining uterine inflammation. In some tissue settings, loss of Foxp3 expression can cause instability in Treg cell lineage commitment, elevated production of proinflammatory cytokines and compromised suppressive function. Whether preterm birth susceptibility is associated with loss of lineage fidelity and adoption of proinflammatory phenotypes in Treg cells is unknown. In this study, we investigated the lineage stability of Treg cells in vivo in pregnant mice using a Foxp3 fate-mapping system and models of preterm birth induced by late-gestation inflammatory challenge with lipopolysaccharide (LPS) or interleukin-1β (IL-1β). Ex-Foxp3-expressing (ex-Foxp3) cells were observed in the uterus-draining lymph nodes (udLNs) in non-pregnant mice and in similar abundance across normal gestation, and a proportion expressed proinflammatory cytokines IFNγ and/or IL-17A. Bulk RNA-sequencing of sorted Treg and ex-Foxp3 cells from late-gestation udLNs revealed substantial loss of the Treg cell lineage program in ex-Foxp3 cells, characterized by reversal in expression of canonical Treg cell genes and pathways. Late gestation LPS or IL-1β administration to induce preterm birth did not expand the ex-Foxp3 cell population in the uDLNs or uterine decidua. We conclude that uterine Treg cells exhibit a high level of lineage stability in pregnancy regardless of proinflammatory challenge. Whether there is any biological or pathophysiological significance of ex-Foxp3 cells in gestational tissues remains to be defined.

An imbalance of the vaginal microbiome and dysregulation of cytokines are associated with spontaneous preterm birth (sPTB). To date, the relationship between the vaginal microbiome, cytokines, and sPTB remains unclear in the Chinese population. Herein, we conducted a nested case-control study using data from a prospective cohort of 749 Chinese women with a singleton pregnancy who were enrolled between 16 and 28 weeks of pregnancy. Cases consisted of individuals experiencing sPTB (n = 38), while controls were selected randomly at a 4:1 ratio to cases (n = 152). Compared to the term group, the sPTB group exhibited significantly increased abundance of vaginal Aerococcus christensenii, Gardnerella swidsinskii, and Lactobacillus iners, along with elevated levels of interleukin (IL)-1β, IL-6, and IL-12p70 in vaginal fluid (P < 0.05). Least absolute shrinkage and selection operator (LASSO) regression identified L. iners, G. swidsinskii, and IL-6 as significant risk factors for sPTB, with adjusted odds ratios (ORs) (95% CI) of 1.57 (1.06-2.34), 1.45 (1.03-2.05), and 2.05 (1.43-2.93), respectively. Finally, a logistic regression model for sPTB was established incorporating L. iners, G. swidsinskii, and IL-6, which yielded an area under the receiver operating characteristic curve (AUC) of 0.73. These findings suggest that alterations in the vaginal microbiome and cytokine levels may contribute to sPTB in the Chinese population.IMPORTANCEPreterm birth (PTB) is the leading cause of death in children under 5 years of age, of which about 70% were spontaneous ones (sPTB); while genitourinary infections are implicated in 25-40% of sPTB cases. Previous studies have revealed some features of vaginal microbiome and cytokines related to sPTB: increased richness and diversity, increased levels of Lactobacillus iners, BV-associated bacteria, low abundance of L. crispatus, and high levels of pro-inflammatory cytokines. However, there were also some inconsistent findings, and little is known in the Chinese population. This study confirmed the correlations between vaginal microbiome, cytokines, and sPTB in Chinese pregnant women. Specifically, elevated vaginal L. iners, G. swidsinskii, and IL-6 levels were significantly associated factors, which may help to identify women at high risk of sPTB.

Distribution of childhood cancer types using the International Classification of Childhood Cancer, third edition classification in a tertiary hospital in northwest Mexico.

Gunshot wounds (GSWs) are the leading cause of death in children. This study defines pediatric firearm wound patterns and fatal organ injury to identify salvageability of injuries. Survivor data were collected from an urban Level I pediatric trauma center and nonsurvivor data were collected from the medical examiner. All GSW patients aged 14 years and younger from 2011 to 2021 were included. Both survivors and nonsurvivors were analyzed for body area wounds. For nonsurvivors, trauma surgeons and medical examiners determined fatal organ injury. Wound patterns and fatal organ injury were compared with existing data on adult wound patterns and fatal organ injury. A total of 165 patients were analyzed, including 148 (90%) survivors. Nonsurvivors were younger (8 ± 4 vs. 10 ± 4 years old, P=0.04). Only 5% of survivors had a tourniquet placed, but none required operative control of hemorrhage. All nonsurvivors suffered head wounds, chest wounds, or both. Nonsurvivors had significantly more head wounds (71%) compared with survivors (9%) (P<0.001). Survivors had significantly more extremity wounds than nonsurvivors (68% vs. 12%, P<0.001). Nonsurvivors had significantly more brain (71% vs. 3%, P<0.001) and heart injuries (24% vs. 1%, P<0.001). No deaths were caused by exsanguination from peripheral vascular injury. Pediatric firearm deaths are largely due to nonsurvivable brain injury. The best opportunity to lower pediatric firearm mortality is to prevent the injury itself, although this needs to be assessed in other cities and settings as well.

In most cases, contaminated food and water sources are the cause of diarrheal disease, which is one of the world's most severe leading causes of child mortality and morbidity. The second most common cause of death for children under five is illness caused by diarrhea. It is curable and also preventable. Diarrhea, transmitted via fecal–oral route, is caused by various pathogens, including bacteria, viruses, protozoa, and helminthes. In developing countries with insufficient sanitation, cleanliness, and access to clean water, cholera is an epidemic that spreads from person to person. A cross-sectional secondary review and quantitative study was done to assess the ten years trend of cholera incidence and mortality as well as relationship between cholera cases and Environmental factors. For this study, secondary data was used. In addition, desk review was conducted to analyze previous study reports, articles and literatures to examine the association between the disease incidences and associated environmental factors in Nepal. The Government of Nepal plan and implement various programs for prevention and treatment, cholera incidence and deaths are still present in the country. Cholera outbreaks continue to occur at different times and places in Nepal, causing serious problems. This study shows that the water Scarcity, open defecation and hand washing practices are still prevalent in Nepal and cholera incidence and related deaths continue to occur

Preterm birth is the leading cause of death in children under five years of age worldwide. The association between preterm birth and long-term outcomes is vaguely known. In very preterm infants, the gut microbiome is highly variable and impacted by the neonatal intensive care unit environment. Our objective was to better understand the crosstalk between the gut microbiome and the host at one month of age in very preterm infants and its impact on neurological outcomes at two years of age. We performed a multi-omics analysis of fecal samples collected in 2011 from 73 very preterm French infants at one month of age, grouped according to their neurodevelopment assessed at two years of age using the Ages & Stages questionnaire. Multi-omics profiling and integrative analyses were performed between 2022 and 2023, including fecal microbiome, metabolome, and host transcriptome characterization using 16S rRNA gene sequencing, LC-MS, and mRNA sequencing, respectively. The gut microbiome of very preterm infants at one month is mostly driven by either Escherichia or Staphylococcus, which are differentially associated with host immune markers (CAMP), metabolomic pathways, notably the energy pathway due to the presence of various nicotinamide adenine dinucleotides (NAD+) and two-year neurodevelopmental outcomes. The gut microbiome at one month of age could be a noninvasive biomarker of gut immaturity and metabolic defects. Escherichia and Staphylococcus proportions were found to be the best indicators of physiological maturity and immaturity, respectively. Escherichia may help the process of intestinal maturation in preterm infants through specific metabolites production and is associated with a better neurodevelopment.

Pneumonia is the leading infectious cause of death in children under five globally. Its prevalence varies by place and time depending on the level of implementation of protective and preventive strategies. Identifying the current burden of childhood pneumonia and its modifiable risk factors is important for health stakeholders to prioritize actions. This study aimed to assess the proportion of pneumonia morbidity and its determinants. A health facility-based cross-sectional study was conducted among 1200 sick children under five years who visited health centers from March to July 2023 in the South Gondar zone, northwest Ethiopia. Two-stage random sampling was used. Data were collected through exit interviews with caregivers and clinical reassessment. Descriptive statistics and binary logistic regression analyses were performed. The proportion of pneumonia morbidity was 28.3%. Behavioral factors such as daily opening of windows, use of a non-improved traditional stove, shortened exclusive breast-feeding, and using soap for hand washing were among the factors associated with pneumonia morbidity in children. The proportion of pneumonia morbidity remains high, with modifiable risk factors identified as significant contributors to childhood pneumonia. To address the high burden of childhood pneumonia in the region, health stakeholders should focus on strengthening community-level behavioral change communication efforts.

Metagenomic sequencing of bronchoalveolar lavage fluid in pediatric pneumonia: A single-center study in Gansu province.

Transitioning from the International Classification of Diseases 10 (ICD-10) to 11 (ICD-11) will enhance the accuracy of health data reporting at the national level, however, certain challenges affect the outcome of such change. To document the experience of Lebanon in transitioning its mortality data from ICD-10 to ICD-11. We collected hospital mortality data from the Ministry of Public Health of Lebanon for 2022 and analysed them based on ICD-10 and ICD-11. We mapped and compared the reported ICD-10 and ICD-11 causes of death using the Analysing Mortality and Causes of Death 3 (ANACoD3) tool. Discrepancies between the frequencies of causes of death between ICD-10 and ICD-11 were most visible in noncommunicable diseases. Although NCDs were the leading causes of death for both systems, the difference was higher in ICD-10 (64.0%) than ICD-11 (41.29%). Seventeen of the 20 leading causes of death generally and 16 of the 20 leading causes of child deaths (0-4 year-olds) were the same for ICD-10 and ICD-11, but with different rankings. The noncommunicable/ communicable disease ratio for Lebanon was 3.4 with ICD-10 and 2.3 with ICD-11, and the usability index was higher for ICD-10 (38.4) than for ICD-11 (36.3). Our findings show that moving from ICD-10 to ICD-11 at the central level can be useful in enhancing the quality of cause of death coding if there is enough data at the central level and if properly monitored by an experienced coder.

Diarrhea is the third leading cause of death in children under five, causing nutritional deficits that hinder growth, cognitive, and academic performance. Each episode before the age of 2 years increases the risk of stunting by 5%. Systematic data, such as sociodemographic, clinical characteristics, and laboratory characteristics, are important for prevention. This descriptive observational study used a retrospective design based on medical records of children with acute diarrhea treated at Dr. Soetomo General Hospital, Surabaya, from 2021 to 2023. A total of 461 subjects met the criteria; 429 underwent electrolyte imbalance testing, 198 were assessed for urea and creatinine levels, and 68 had their acid-base balance evaluated. A total of 288 subjects (62.5%) were male children; 262 patients (75%) were 0-12 months old; 253 (61%) had good nutritional status; 339 (73.5%) underwent therapy for less than 1 week; and 402 patients (65%) recovered. A total of 40% experienced mild-moderate and severe dehydration with neurologic (16.4%) and respiration comorbidities (16.2%). Electrolyte disturbances included hyponatremia (33.1%), hypokalemia (12.1%), hyperchloremia (50.2%), increased urea (28.3%), abnormal creatinine (35.4%), hypobicarbonate (75%), and acidosis (63.2%). Therefore, early detection and appropriate management are essential to mitigate further complications and improve recovery outcomes.